Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Serum concentrations of lipoproteins, apolipoprotein A-I (Apo A-I), androgens, including biologically active free testosterone (free T), and sex hormone binding globulin (SHBG) and their associations were studied in 3 groups of men of different physical fitness and risk of CHD, consisting of male CHD patients, joggers and healthy controls. Of the 3 study groups, men with angiographically assessed CHD had the lowest HDL-C (P less than 0.002) and highest LDL-C and triglyceride (TG) levels (P = 0.05 and P less than 0.001) and lower 5 alpha-dihydrotestosterone (5 alpha-DHT) levels than joggers (P less than 0.02). Joggers had the highest serum high density lipoprotein cholesterol (HDL-C), Apo A-I and SHBG levels and lowest serum low density lipoprotein cholesterol (LDL-C) compared to the other groups (P less than 0.01). In correlation analysis 5 alpha-DHT was the most significant positive determinant of HDL-C and Apo A-I levels in CHD patients (r = 0.56 and r = 0.55, respectively, P less than 0.05). Moreover, SHBG was significantly positively correlated to both HDL-C and Apo A-I levels in patients, in the whole study group and in healthy men separately (r = 0.37-0.52, P less than 0.01). These significant correlations were also confirmed when age variation and differences in body mass index and smoking were controlled in multivariate analysis and in addition, in multivariate analysis both serum free and total testosterone were inversely related to serum triglyceride (TG) levels.(ABSTRACT TRUNCATED AT 250 WORDS)
Atherosclerosis 1987 Oct
PMID:Serum lipoproteins, sex hormones and sex hormone binding globulin in middle-aged men of different physical fitness and risk of coronary heart disease. 367 10

To assess the direct effect of androgen on the development of atherosclerosis, we investigated the effect of androgen and its receptor expression in rat vascular smooth muscle cells (VSMC) isolated from rat aorta. We detected the androgen receptor mRNA in VSMC by reverse transcription of the total RNA coupled with amplification of the resulting cDNA by polymerase chain reaction. Binding studies revealed the presence of a single class of binding sites for testosterone (Kd 7.37 nM, Bmax 10.59 fmol/mg protein) and dihydrotestosterone (DHT; Kd 4.89 nM, Bmax 11.37 fmol/mg protein) in VSMC. Measurement of 5 alpha-reductase activity suggested that testosterone is converted to DHT in VSMC (Km 0.36 microM, Vmax 623 fmol/mg protein/h). Moreover, in the present study, DHT significantly stimulated DNA synthesis of VSMC (120-160% of control). The mitogenic activity of testosterone is much less potent than that of DHT. Considering these results, we concluded that androgen may directly accelerate atherosclerosis by stimulating the proliferation of VSMC.
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PMID:Androgen receptors, 5 alpha-reductase activity and androgen-dependent proliferation of vascular smooth muscle cells. 804 46

Serum apolipoprotein AI (apoAI) levels correlate with the risk of developing atherosclerosis. Previous studies have suggested that dehydroepiandrosterone (DHEA) lowers high-density lipoprotein (HDL)-cholesterol levels. We investigated whether or not DHEA may lower HDL-cholesterol levels by suppressing apoAI gene transcription in hepatocytes. ApoAI mRNA levels, assessed by Northern blotting, were suppressed in HepG2 cells treated with DHEA (34%) (10 microg/mL) or testosterone (36%) (T, 1 microg/mL). Estradiol alone (E2, 1 microg/mL) had relatively little effect on apoAI mRNA levels, while E2 in combination with DHEA prevented a decrease in apoAI mRNA levels compared to DHEA alone. To determine whether these effects were due to changes in apoAI gene transcription, HepG2 cells were transfected with a plasmid carrying the full-length promoter of the rat apoAI gene ligated into a chloramphenicol acetyltransferase (CAT) reporter construct. The plasmid pCMV.SPORT-beta-gal was included in each transfection to normalize the data to transfection efficiency. Cells were then cultured in the presence or absence of DHEA (10 microg/mL), T (1 microg/mL), 17alpha-methyltestosterone (MTT, 1 microg/mL), 5alpha-dihydrotestosterone (DHT, 1 microg/mL), E2 (1 microg/mL), or a combination of DHEA plus E2, T plus E2, MTT plus E2, and DHT plus E2, for 24 hours. CAT activity, relative to beta-galactosidase activity, was reduced by 19.6%, 57.6%, 38.6%, and 54.6% with DHEA, T, DHT, and MTT addition, respectively. E2 increased CAT activity by 43.8%. When the androgens (ie, DHEA, T, DHT, or MTT) were combined with E2, apoAI promoter activity was suppressed. We conclude, therefore, that androgens downregulate apoAI promoter activity in the presence or absence of E2. However, the changes in mRNA levels do not always reflect changes in promoter activity, suggesting that these steroids may have additional post-transcriptional effects on steady-state apoAI mRNA levels. It remains to be established if the transcriptional effects we observed are mediated through an androgen response element.
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PMID:Effects of dehydroepiandrosterone on rat apolipoprotein AI gene expression in the human hepatoma cell line, HepG2. 1188 77